A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma (iMATRIX GLO)

A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).

Study Overview

• Status: Recruiting
• Conditions: Mature B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Glofitamab; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CO43810 https://forpatients.roche.com; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Queensland Children?s Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Perth Children's Hospital
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Rigshospitalet; Ny Medicin til Børn med Kræft
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Hôpital Pellegrin; Service d'oncologie pédiatrique
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Muenster, Germany, 48149
    • Recruiting
    • Universitaetsklinikum Muenster; Paedriatrische Haematologie und Onkologie
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00165
      • Recruiting
      • IRCCS Ospedale Pediatrico Bambino Gesù; Clinical trial center - Pad. Salviati 1 floor
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Recruiting
      • Ospedaliera Ospedale Infantile Regina Margherita; Oncoematologia Pediatrica-Centro Trapianti Cellule
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03080
    • Completed
    • Seoul National University Hospital- Pediatric Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital Infantil Universitario Niño Jesus; Servicio de Onco-hematologia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Children's Hospital of Alabama
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
    • Oakland, California, United States, 94611
      • Recruiting
      • Kaiser Permanente Oakland Medical Center
    • Roseville, California, United States, 95661
      • Recruiting
      • Kaiser Permanente - Roseville
    • Santa Clara, California, United States, 95051
      • Active, not recruiting
      • Kaiser Permanente - Santa Clara
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins University
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Childrens Mercy Hosp & Clinics
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • MSKCC
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 6 months to < 18 years at the time of signing Informed Consent for Part 1 and Cohort B of the study, and age 6 months to ≤ 30 years old at the time of signing Informed Consent for Part 2 of the study
• Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B
• Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B
• Measurable disease, defined as: At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension; or percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates
• Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales: Participants < 16 years old: Lansky Performance Status ≥ 50%; Participants ≥ 16 years old: Karnofsky Performance Status ≥ 50%
• Adequate bone marrow, liver, and renal function
• Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV)
• Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ≥200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
• Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
• Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods

Exclusion Criteria:

• Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
• Receipt of glofitamab prior to study enrollment
• Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
• Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
• Participants with active infections which are not resolved prior to Day 1 of Cycle 1
• Prior solid organ transplantation
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or chronic active Epstein-Barr viral infection (CAEBV)
• Active autoimmune disease requiring treatment
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products, except if the participant was able to safely receive it after initial administration (consider consultation with Medical Monitor)
• History of confirmed progressive multifocal leukoencephalopathy
• Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment
• Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).	Drug: Obinutuzumab; Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days); Drug: Glofitamab; Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3 Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter (Cycle length = 21 days); Drug: Rituximab; Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days); Drug: Ifosfamide; Participants will receive IV ifosfamide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days); Drug: Carboplatin; Participants will receive IV carboplatin on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days); Drug: Etoposide; Participants will receive IV etoposide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days); Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events
Experimental: Arm B; Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).	Drug: Obinutuzumab; Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days); Drug: Glofitamab; Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3 Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter (Cycle length = 21 days); Drug: Tocilizumab; Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A)	Up to 3 treatment cycles (cycle length = 21 days)
Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A)	Up to 3 treatment cycles (cycle length = 21 days)
Serum concentration of glofitamab monotherapy (Arm B)	Up to 12 treatment cycles (Arm B) (cycle length = 21 days)
Percentage of participants with adverse events (AEs) (Arm A)	Approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) (Arms A and B)	Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A)	Up to 3 treatment cycles (cycle length = 21 days)
Serum concentration of obinutuzumab (Arms A and B)	Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days)
Serum concentration of rituximab (Arm A)	Up to 3 treatment cycles (cycle length = 21 days)
Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B)	Up to 3 treatment cycles (cycle length = 21 days)
Duration of complete response (DOCR) (Arm A)	From the first occurrence of a documented complete response (CR) to documented disease progression or death from any cause (whichever occurs first) (approximately 3 years)
Progression-free survival (PFS) (Arm A)	From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 3 years)
Event-free survival (EFS) (Arm A)	From enrollment to the first occurrence of disease progression, death from any cause, or start of new anti-lymphoma therapy (not including planned hematopoietic stem cell transplantation (HSCT)) (approximately 3 years)
Overall survival (OS) (Arms A and B)	From the first study treatment to the date of death from any cause (Arm A = approximately 3 years, Arm B = approximately 4 years)
Duration of response (DOR) (Arm B)	From the first occurrence of a documented CR or partial response (PR) until documented disease progression or death from any cause, whichever occurs first (approximately 4 years)
Percentage of participants with AEs (arm B)	Approximately 3 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-LaRoche

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2022
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; Pediatrics; B-NHL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Ifosfamide; Rituximab; Obinutuzumab
• Other Study ID Numbers: CO43810

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No